Aggression, a nearly universal feature of the behavior of social animals, is used for access to food and shelter, for protection from predation and for selection of mates. Little is known of the neural mechanisms that underlie the behavior, although most investigators agree that neurohormones play important roles in aggression. Until recently it was not well known that fighting behavior exists in common laboratory strains of the fruit fly, Drosophila melanogaster. With the genome sequenced and a wealth of genetic tools available, fruit flies can serve as a unique experimental model for the study of aggression. In this application, fruit flies will be used to examine the roles of amines and peptides in aggression. Using a simplified protocol that allows reliable fighting behavior to be seen between pairs of both male and female flies, this application has two Specific Aims. Aim I. To observe the behavioral consequences of altering amine transmitter function or release on aggression. Towards this goal, we will: (i) use classical amine mutant fly lines; (ii) use the GAL4/UAS system to drive the expression of a mutant form of the protein dynamin (involved in synaptic vesicle recycling) in amine-containing neurons in fly brains, a manipulation that alllows the turning off of amine neurons while flies are fighting; and (iii) use a newly developed method that allows the selective turning on of amine neurons while flies are fighting. The latter two manipulations are not now possible with other species of animals. We also propose beginning studies examining amine neuron circuitry in fly brains. Aim II. To examine the behavioral consequences of selectively interfering with neuropeptide release in neurons co-releasing peptides and classical transmitter compounds. Towards this goal we will: (i) use mass spectrometry to identify and sequence the peptides in fly brains; (ii) use mass spectrometry combined with labeling of neurons to identify peptides found co-localized with amines and other transmitters; and (iii) use genetic tools to selectively interfere with peptide release from neurons and observe the effects on aggression. Relevance: Violence in human society is a serious problem that must have a biological basis. Little is known, however, about the neuronal roots of aggression. These studies with fruit flies-allow unique glimpses, not available with other species at the present time, of the roles served by neurohormones;like amines and peptides that are known to be important in aggression in all species of animals, including man.